title: Design and synthesis of naphthalenic derivatives as new ligands at the melatonin binding site MT3.
abstract: Naphthalenic analogs of MCA-NAT (5-methoxycarbonylamino-N-acetyltryptamine) have been synthesized and evaluated as melatonin receptor ligands. Introduction of a methoxycarbonylamino substituent at the C-7 position of the naphthalenic nucleus yields MT3 selective ligands. This selectivity can be modulated with suitable variations of the C-7 position and the acyl group on the C-1 side chain. We identified new series of compounds with affinity for the MT3 binding site in the nanomolar range, and singled out a selective ligand, (N-[2-(7-methylsulfamoyl-naphth-1-yl)ethyl]acetamide (17), with a Ki of 4.9 nM and selectivity of 1024 and 2040 versus MT1 and MT2 receptors respectively.
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Leclerc
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ettaoussi
authors.forename: Marouan
authors.initials: M
authors.lastname: Rami
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Jean Albert
authors.initials: JA
authors.lastname: Boutin
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Daniel-Henri
authors.initials: DH
authors.lastname: Caignard
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.forename: Saïd
authors.initials: S
authors.lastname: Yous
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D015195:Drug Design; D008024:Ligands; D008550:Melatonin / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044094:Receptors, Melatonin / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D009281:Naphthalenes; D044094:Receptors, Melatonin; D008550:Melatonin